PMID- 16137723 OWN - NLM STAT- MEDLINE DCOM- 20060117 LR - 20131121 IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 49 IP - 8 DP - 2005 Dec TI - Repeated exposure to Delta(9)-tetrahydrocannabinol alters heroin-induced locomotor sensitisation and Fos-immunoreactivity. PG - 1189-200 AB - The present study examined the effect of chronic exposure to Delta(9)-tetrahydrocannabinol (THC) on heroin-induced locomotor sensitisation and Fos-immunoreactivity (Fos-IR). Adult male albino Wistar rats (n=60) were injected intraperitoneally (i.p.) 21 times with vehicle, 0.05, 0.5, or 5.0mg/kg THC (once every 48 h for 41 days). Locomotor activity was assessed for 180 min on pre-exposure days 1, 21, and 41. Following a 2-week washout period, rats were divided into five equal groups (n=12) and injected subcutaneously (s.c.) with vehicle or heroin (0.5mg/kg). Locomotor activity was recorded for 240 min. In drug-naive rats, heroin significantly increased locomotor activity. THC pre-exposure further increased heroin-induced locomotion. After an interval of 2 weeks, rats pre-exposed to vehicle and 5.0mg/kg THC in the first part of the experiment were randomly assigned to one of four treatment groups (n=6) and injected s.c. with vehicle or 0.5mg/kg heroin and perfused 2h later. Fos-IR was examined in several brain regions. Acute heroin increased Fos-IR in drug-naive rats in the caudate-putamen (CPu; central, medial and dorsomedial regions), nucleus accumbens (NAC; core and shell regions), bed nucleus of the stria terminalis (BNST), lateral septum, central nucleus of the amygdala (CEA), periaqueductal grey (PAG; dorsolateral, dorsomedial, and lateral), and the Edinger-Westphal nucleus. Pre-exposure to THC significantly increased heroin-induced Fos-IR in the dorsomedial CPu and the NAC (core). Conversely, THC pre-exposure reduced heroin-induced Fos-IR in the BNST, CEA, and the PAG (dorsolateral and lateral). The present study demonstrates that THC pre-exposure increases the locomotor stimulating effects of heroin and provides new evidence for the neural correlates that may underlie cannabinoid and opioid cross-sensitisation. FAU - Singh, M E AU - Singh ME AD - School of Psychology, University of New England, Armidale, NSW 2351, Australia. FAU - McGregor, I S AU - McGregor IS FAU - Mallet, P E AU - Mallet PE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050830 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Hallucinogens) RN - 0 (Narcotics) RN - 70D95007SX (Heroin) RN - 7J8897W37S (Dronabinol) SB - IM MH - Animals MH - Brain/drug effects MH - Brain Chemistry/drug effects MH - Dose-Response Relationship, Drug MH - Dronabinol/administration & dosage/*pharmacology MH - Gene Expression/drug effects MH - Genes, fos/*genetics MH - Hallucinogens/administration & dosage/*pharmacology MH - Heroin/*pharmacology MH - Injections, Intraperitoneal MH - Injections, Subcutaneous MH - Male MH - Motor Activity/*drug effects MH - Narcotics/*pharmacology MH - Rats MH - Rats, Wistar EDAT- 2005/09/03 09:00 MHDA- 2006/01/18 09:00 CRDT- 2005/09/03 09:00 PHST- 2004/12/16 00:00 [received] PHST- 2005/07/13 00:00 [revised] PHST- 2005/07/14 00:00 [accepted] PHST- 2005/09/03 09:00 [pubmed] PHST- 2006/01/18 09:00 [medline] PHST- 2005/09/03 09:00 [entrez] AID - S0028-3908(05)00262-5 [pii] AID - 10.1016/j.neuropharm.2005.07.008 [doi] PST - ppublish SO - Neuropharmacology. 2005 Dec;49(8):1189-200. doi: 10.1016/j.neuropharm.2005.07.008. Epub 2005 Aug 30.